Development of Lymphopenia during Therapy with Immune Checkpoint Inhibitors Is Associated with Poor Outcome in Metastatic Cutaneous Melanoma

SIMPLE SUMMARY: Predictive markers are necessary for immune checkpoint inhibitor (ICI) therapy. The aim of our retrospective study was to investigate the relationship between the occurrence of lymphopenia under ICI and disease outcome. A total of 116 patients with metastatic melanoma who received ICI therapy with normal lymphocyte counts at baseline were analyzed. Lymphopenia occurred in 42.2% of patients with a mean onset after 17 weeks (range 1–180 weeks). The occurrence of lymphopenia during immunotherapy was significantly associated with a shorter PFS and OS. Patients who developed lymphopenia (n = 49) had a mean PFS of 13.3 months (range 1–67 months) compared to 16.9 months (range 1–73 months) for patients who did not develop lymphopenia (n = 67; p = 0.025). Similarly, patients with lymphopenia had a significantly shorter OS of 28.1 months (range 2–70 months) compared with 36.8 months (range 4–106 months) in patients who did not develop lymphopenia (p = 0.01). ABSTRACT: Predictive markers for immune checkpoint inhibitor (ICI) therapy are needed. Thus, baseline blood counts have been investigated as biomarkers, showing that lymphopenia at the start of therapy with (ICI) is associated with a worse outcome in metastatic melanoma. We investigated the relationship between the occurrence of lymphopenia under ICI and disease outcome. Patients with metastatic melanoma who had undergone therapy with ICI were identified in our database. Only patients with a normal lymphocyte count at baseline were included in this retrospective study. Progression-free survival (PFS) and overall survival (OS) were compared between patients in which lymphopenia occurred during ICI therapy and those who did not develop lymphopenia. In total, 116 patients were analyzed. Lymphopenia occurred in 42.2% of patients, with a mean onset after 17 weeks (range 1–180 weeks). The occurrence of lymphopenia during immunotherapy was significantly associated with a shorter PFS and OS. Patients who developed lymphopenia (n = 49) had a mean PFS of 13.3 months (range 1–67 months) compared to 16.9 months (range 1–73 months) for patients who did not develop lymphopenia (n = 67; p = 0.025). Similarly, patients with lymphopenia had a significantly shorter OS of 28.1 months (range 2–70 months) compared with 36.8 months (range 4–106 months) in patients who did not develop lymphopenia (p = 0.01). Patients with metastatic melanoma who develop lymphopenia during ICI therapy have a worse prognosis with significantly shorter PFS and OS compared with patients who do not develop lymphopenia.